Ghrelin impedes oxidative stress induced intestinal epithelial cell apoptosis through varying signaling pathways
DOI:
https://doi.org/10.48111/2022.01.02Keywords:
Ghrelin, Intestinal apoptosis, signaling pathways, Intestinal epithelial cells, Intestinal tractAbstract
Background: Ghrelin, a gut brain peptide, has been primarily studied in the regulation of body weight homeostasis. Recent studies indicate, however, that it has potent anti-apoptotic effects in various cell types and exogenous ghrelin prevents gastric mucosa from ethanol-induced ulcer formation. Given ghrelin is cytoprotective, here we hypothesized ghrelin’s anti-apoptotic effect in intestinal epithelial cells when exposed to severe oxidative stress, which plays a key role in the pathogenesis of various intestinal disorders.
Materials & Methods: Intestinal epithelial cells, FHs74Int, IEC-6 and Caco-2 were used to assess anti-apoptotic effects of ghrelin following H2O2 treatment by TUNEL technique and flowcytometric analyses. In addition, mechanisms responsible for these effects were explored in relation to relevant signaling pathways including PI3K/Akt pathway and cytochrome ‘c’ dependent caspase-3 activation. PI3K/Akt and mitochondrial cytochrome ‘c’ release was assessed by western analysis and caspase-3 activity was determined by ELISA and Immunoflorescence.
Results: H2O2 potently increases the intestinal epithelial apoptosis and necrosis. Ghrelin inhibits intestinal epithelial cell apoptosis through growth hormone secretagogue receptors (GHS-Rs). Further, ghrelin’s anti-apoptotic effect against H2O2 –induced apoptosis is associated with activation of PI3K/Akt, inhibition of mitochondrial cytochrome-c release and like wise inhibition of caspase-3 activation.
Conclusion: In aggregate, our findings suggest that ghrelin inhibits oxidative stress-induced apoptosis in intestinal epithelial cells and hence might serve as a therapeutic strategy in states associated with intestinal mucosal injury, where oxidative stress plays a central role.
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